Miniaturization continues to be an enabling technology in bioinstrumentation that offers key advantages to research in life sciences and pharmaceuticals. Miniaturization provides significant cost savings from low consumption of reagents, with potential time savings from faster reaction rates in methods involving heterogeneous solid supports. As a result, data throughput can be significantly increased without an associated increase in costs.
Efforts on miniaturization in bioinstrumentation have delivered a number of revolutionary tools and opened a new venue in life science and pharmaceutical research. Notably, miniaturization enabled large-scale analysis of biological samples at a lower cost, faster speed and simpler operation, and brought about the era of ‘-omics’. A well-known example of a miniaturized device is a DNA microarray. It allows for a large-scale parallel analysis or reaction of samples in a relatively short time and at a low cost. Efforts are currently taken to miniaturize the commonly used multiwell plate (also called “micro-titer Plate®”). By means of automation of sample handling high-throughput screening can be performed. It has been proposed to extend the respective miniaturization approach by disposing drops of cells onto a substrate, so that they are substantially arranged in a monolayer (cf. International Patent Application WO 2004/111610).
A problem not only occurring at solid-water, but also at air-water and, where applicable, oil-water interfaces is protein adsorption. Recently, Roach et al. (Anal. Chem. (2005), 77, 785) characterized non-specific protein adsorption at the aqueous-perfluorocarbon interface, as well as ways to control adsorption. In their work, an aqueous droplet of protein and enzyme was encapsulated by perfluorocarbon liquid containing perfluorocarbon-ethylene glycol surfactants. The perfluorocarbon liquid-aqueous interface minimized non-specific adsorption of fibrinogen and bovine serum albumin at the interface. The activities of ribonuclease A and alkaline phosphatase at nanoliter scale surrounded by the perfluorocarbon-aqueous interface were identical to those at the bulk scale. The interface between perfluorocarbon liquid and aqueous solution, particularly in embodiments where for instance a perfluorocarbon-ethylene glycol surfactant is present, provides a biocompatible surface in addition to minimizing evaporation of the aqueous solution. Perfluorocarbon liquid is known to provide one of the most biocompatible interfaces among water-immiscible liquids.
A further problem in the use of microdevices, particularly during incubation at for instance 37° C., prolonged storage and extended sample preparation using for instance large numbers of multiwell plates for screening purposes is evaporation. Currently used means to overcome this problem are the use of multiwell-plate covers or seal-strips, stacking, the use of closed microchips and the optimization of assay protocols in order to minimize waiting time. Evaporation is of particular practical concern, since it can falsify data if it occurs unevenly across multiwell plates.
The manipulation of droplets has recently received considerable interest due to the possibility of isolating and handling volumes down to the picoliter/femtoliter range (cf. e.g. International Patent Application WO 2004/030820). Biochemical reactions have for instance been carried out in emulsion droplets (Griffiths, A D, & Tawfik, D S, Trends in Biotechnology (2006) 24, 9, 395-402). Several lab-on-a-chip (LOC), micro total analysis (μTAS), and biological microelectromechanical systems (BioMEMS) have been developed for moving, merging/mixing, splitting, and heating of droplets on surfaces, such as electrowetting-on-dielectric (EWOD) [Pollack, M. G. et al., Appl. Phys. Lett. (2000), 77, 1725-1726], surface acoustic waves (SAW) [Wixforth, A. et al., mstnews (2002), 5, 42-43], dielectrophoresis [Cascoyne, P. R. C. et al., Lab-on-a-Chip (2004), 4, 299-309], and locally asymmetric environments [Daniel, S. et al., Langmuir (2005), 21, 4240-4228]. These methods are however not well suited for methods with a sequence of steps, such as separating, purifying and isolating starting material and/or reaction products from crude or complex mixtures. Such steps may, for example, require rinsing or washing, which can presently only be carried out in multiwell plates, using e.g. automated standard laboratory robots. In order to circumvent these disadvantages, ELISA platforms with microcapillaries and microchannels have been employed (Song, J M. & Vo-Dinh, T, Analytica Chimica Acta (2004), 507, 115-121; Herrmann, M, et al., Lab-on-a-Chip (2006) 6, 555-560). Such platforms are however more cumbersome and expensive, as well as less flexible and convenient to use.
Accordingly it is an object of the present invention to provide an apparatus and a method for processing a chemical and/or biological sample which avoids the above discussed disadvantages.